Tyrosine kinase receptor indistinguishable from the c- met protein

• Published in: Nature (London) 1989-05, Vol.339 (6220), p.155-156
• Main Authors: Giordano, S, Ponzetto, C, Renzo, M. F. Di, Cooper, C. S, Comoglio, P. M
• Format: Article
• Language: English
• Subjects: Biochemistry; Biological and medical sciences; Cancer; Cell Line; Cell receptors; Cell structures and functions; Fundamental and applied biological sciences. Psychology; Gene Amplification; Humanities and Social Sciences; Humans; letter; Molecular and cellular biology; multidisciplinary; Protein-Tyrosine Kinases - chemistry; Proteins; Proto-Oncogene Proteins - chemistry; Proto-Oncogene Proteins c-met; Receptor, Epidermal Growth Factor; Science; Science (multidisciplinary); Stomach Neoplasms - metabolism; Tumors
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/339155a0

GROWTH factor receptors with protein tyrosine kinase activity are central to the control of proliferation of both normal and malignant cells 1–3 . Using anti-phosphotyrosine antibodies 4 , we have previously identified a transmembrane glycoprotein with abnormally high protein tyrosine kinase activity in a human gastric tumour cell line (GTL-16) 5,6 . Electrophoresis under non-reducing conditions revealed that this kinase (relative molecular mass 145,000 (145 K)) is disulphide-linked to a 50K chain in an αβ-complex of 190K (p190). From its novel two-chain structure, we deduced that p190 was the prototype of a new class of tyrosine kinase receptors. We now show that p190 is indistinguishable from the protein encoded by the c- met protooncogene and that the αβ-subunit structure is conserved in other human cell lines. We also show that the high level of p190 found in the GTL-16 cell line is accompanied by amplification and overexpression of c- met . This provides the first example of a functional alteration of c- met in a human tumour cell line.